PMID- 35923800
OWN - NLM
STAT- MEDLINE
DCOM- 20220805
LR  - 20220817
IS  - 2235-2988 (Electronic)
IS  - 2235-2988 (Linking)
VI  - 12
DP  - 2022
TI  - Inhibition of Glycolysis Impairs Retinoic Acid-Inducible Gene I-Mediated 
      Antiviral Responses in Primary Human Dendritic Cells.
PG  - 910864
LID - 10.3389/fcimb.2022.910864 [doi]
LID - 910864
AB  - Dendritic cells (DCs) are important mediators of the induction and regulation of 
      adaptive immune responses following microbial infection and inflammation. Sensing 
      environmental danger signals including viruses, microbial products, or 
      inflammatory stimuli by DCs leads to the rapid transition from a resting state to 
      an activated mature state. DC maturation involves enhanced capturing and 
      processing of antigens for presentation by major histocompatibility complex (MHC) 
      class I and class II, upregulation of chemokines and their receptors, cytokines 
      and costimulatory molecules, and migration to lymphoid tissues where they prime 
      naive T cells. Orchestrating a cellular response to environmental threats 
      requires a high bioenergetic cost that accompanies the metabolic reprogramming of 
      DCs during activation. We previously demonstrated that DCs undergo a striking 
      functional transition after stimulation of the retinoic acid-inducible gene I 
      (RIG-I) pathway with a synthetic 5' triphosphate containing RNA (termed M8), 
      consisting of the upregulation of interferon (IFN)-stimulated antiviral genes, 
      increased DC phagocytosis, activation of a proinflammatory phenotype, and 
      induction of markers associated with immunogenic cell death. In the present 
      study, we set out to determine the metabolic changes associated with RIG-I 
      stimulation by M8. The rate of glycolysis in primary human DCs was increased in 
      response to RIG-I activation, and glycolytic reprogramming was an essential 
      requirement for DC activation. Pharmacological inhibition of glycolysis in 
      monocyte-derived dendritic cells (MoDCs) impaired type I IFN induction and 
      signaling by disrupting the TBK1-IRF3-STAT1 axis, thereby countering the 
      antiviral activity induced by M8. Functionally, the impaired IFN response 
      resulted in enhanced viral replication of dengue, coronavirus 229E, and Coxsackie 
      B5.
CI  - Copyright (c) 2022 Zevini, Palermo, Di Carlo, Alexandridi, Rinaldo, Paone, 
      Cutruzzola, Etna, Coccia, Olagnier and Hiscott.
FAU - Zevini, Alessandra
AU  - Zevini A
AD  - Pasteur Laboratories, Istituto Pasteur Italia - Fondazione Cenci Bolognetti, 
      Rome, Italy.
FAU - Palermo, Enrico
AU  - Palermo E
AD  - Pasteur Laboratories, Istituto Pasteur Italia - Fondazione Cenci Bolognetti, 
      Rome, Italy.
FAU - Di Carlo, Daniele
AU  - Di Carlo D
AD  - Pasteur Laboratories, Istituto Pasteur Italia - Fondazione Cenci Bolognetti, 
      Rome, Italy.
FAU - Alexandridi, Magdalini
AU  - Alexandridi M
AD  - Pasteur Laboratories, Istituto Pasteur Italia - Fondazione Cenci Bolognetti, 
      Rome, Italy.
FAU - Rinaldo, Serena
AU  - Rinaldo S
AD  - Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of 
      Rome, Rome, Italy.
FAU - Paone, Alessio
AU  - Paone A
AD  - Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of 
      Rome, Rome, Italy.
FAU - Cutruzzola, Francesca
AU  - Cutruzzola F
AD  - Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of 
      Rome, Rome, Italy.
FAU - Etna, Marilena P
AU  - Etna MP
AD  - Department of Infectious Diseases, Istituto Superiore Sanita, Rome, Italy.
FAU - Coccia, Eliana M
AU  - Coccia EM
AD  - Department of Infectious Diseases, Istituto Superiore Sanita, Rome, Italy.
FAU - Olagnier, David
AU  - Olagnier D
AD  - Department of Biomedicine, Aarhus University, Aarhus, Denmark.
FAU - Hiscott, John
AU  - Hiscott J
AD  - Pasteur Laboratories, Istituto Pasteur Italia - Fondazione Cenci Bolognetti, 
      Rome, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220718
PL  - Switzerland
TA  - Front Cell Infect Microbiol
JT  - Frontiers in cellular and infection microbiology
JID - 101585359
RN  - 0 (Antiviral Agents)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - *Antiviral Agents/metabolism
MH  - *Dendritic Cells
MH  - Glycolysis
MH  - Humans
MH  - Monocytes
MH  - Tretinoin/metabolism
PMC - PMC9339606
OTO - NOTNLM
OT  - RIG-I
OT  - glycolysis
OT  - immunometabolism
OT  - innate immunity
OT  - moDC
OT  - viral infection
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/08/05 06:00
MHDA- 2022/08/06 06:00
PMCR- 2022/01/01
CRDT- 2022/08/04 02:25
PHST- 2022/04/01 00:00 [received]
PHST- 2022/06/17 00:00 [accepted]
PHST- 2022/08/04 02:25 [entrez]
PHST- 2022/08/05 06:00 [pubmed]
PHST- 2022/08/06 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fcimb.2022.910864 [doi]
PST - epublish
SO  - Front Cell Infect Microbiol. 2022 Jul 18;12:910864. doi: 
      10.3389/fcimb.2022.910864. eCollection 2022.